肠道微生物调控宿主食欲的研究进展

肠道微生物与宿主代谢相互作用,可调节机体的生理功能。宿主机体中存在"微生物-肠道-大脑轴",肠道菌群可通过多种途径影响中枢神经系统,进而对宿主摄食等行为产生影响。食物中不易被宿主消化吸收的膳食纤维等营养物质,被肠道微生物发酵可产生多种代谢产物,这些代谢产物作为信号分子可通过不同途径介导中枢神经系统,进而调控宿主食欲。本文主要综述了肠道微生物及其代谢产物对中枢神经系统与宿主食欲的影响及其可能的调控途径与机制,以加深肠道微生物在调控宿主食欲方面的新认识。     

动物宿主——肠道微生物代谢轴研究进展

肠道中栖息着数量庞大且复杂多样的微生物菌群,在维持宿主肠道微环境稳态中发挥重要作用。微生物菌群可以利用宿主肠道的营养素,发酵产生代谢产物,与宿主机体形成宿主—微生物代谢轴(host-microbe metabolic axis)。该代谢轴既能影响营养素吸收和能量代谢,又可调控宿主各项生理过程。本文主要阐述宿主-肠道微生物代谢轴的概念、肠-肝轴、肠-脑轴、肠道微生物与宿主肠道代谢轴的互作以及对机体健康的影响。     

猪肠道微生物与机体脂质代谢研究进展

肠道微生物在调控宿主脂质代谢中发挥重要作用.猪是一种易沉积脂肪的动物,但其很少发生代谢性疾病,其肠道核心菌群及代谢产物被认为是主导该生理现象的原因之一.本文系统综述了猪肠道微生物与脂质代谢的关系,分析了微生物代谢产物包括短链脂肪酸、胆碱代谢物和胆汁酸等对脂质代谢影响作用,以期洞悉肠道微生物调控宿主脂质代谢的潜在机制.旨在为猪生产中机体脂质沉积调控提供思路,为人类脂质代谢紊乱所引起的代谢性疾病研究提供可用模型和借鉴.     

肠道微生物和肠-脑轴在肥胖发展中的作用

肥胖和相关代谢综合征已成为全球最突出的健康问题之一,肠道微生物已被证明参与肥胖的发展,并可能对肥胖的发展和其干预治疗等提供重要的见解。最近的研究表明,肠道微生物和大脑的相互作用可能是肥胖的后果或解释因素,肠-脑轴是它们相互作用的联络枢纽。此外,肠道微生物可以通过肠道激素（包括ghrelin）以及迷走神经连接（影响能量消耗和CNS中与饮食行为相关的区域）来影响肠-脑轴,从而改变宿主行为。同时,肠道微生物代谢物和其产物还可以充当信号分子并调节肠内分泌细胞的激素分泌,如GLP1和PYY,从而调节食欲、肠道运动、能量吸收和储存以及能量消耗等摄食相关行为,进而影响肥胖的发展。所以,理解这些信号和激素作用并从药理学方法增强它们,可能为治疗肥胖提供一种重要的途径。     

肠道上皮与肠道微生物相互作用的研究现状

肠道上皮是肠上皮细胞及其分泌物有机构成的黏膜界面。随着技术的进步和对肠道菌群作用的逐渐重视,研究者对肠道上皮与肠道微生物相互作用的认识也不断深入。研究表明,肠道上皮调节并维持肠道微生物的定殖与分布,肠道微生物也影响肠道上皮的多种屏障功能,二者通过一系列细胞分子机制紧密联系,共同维持肠道稳态。此外,其过程中产生的宿主-肠道菌群共代谢物被发现可以反映宿主的生理病理状态,作为指标被应用于临床疾病诊断、治疗效果评估和预后推测。本文基于近年的研究,综述了肠道上皮与肠道微生物的相互作用及其细胞分子机制,为进一步研究和临床应用总结了理论基础,并探讨了未来可能的研究方向。     

microRNA 对宿主和肠道微生物互作的调控

摘要:肠道内环境是宿主和肠道微生物菌群互作的结果,肠道菌群一方面通过抗原物质调节肠道组织的免疫稳定,另一方面,肠道菌群参与糖、脂、蛋白质代谢,产生的代谢产物能够调控细菌营养代谢、群体结构和肠道组织的营养吸收等。microRNA是宿主细胞内调控基因表达的重要因子,肠道微生物菌群不仅调控宿主mRNA的转录,同时也影响某些基因的转录后修饰。研究表明,肠道菌群通过与宿主肠道组织互作,调节肠上皮组织内某些参与炎症应答和屏障功能的microRNA 的表达。本文介绍了肠道微生物与宿主互作的基本内容,对microRNA在肠道微生物与宿主互作和肠道健康中的调节进行综述。     

哺乳动物肠道微生物与碳水化合物的互作及其影响

肠道微生物具有调节宿主营养、免疫以及能量代谢等生理功能。饮食是影响哺乳动物的肠道微生物的一个重要因素。碳水化合物是哺乳动物食物能量的主要来源,因此研究肠道微生物与碳水化合物的代谢之间的关系及其影响具有重要意义。基于近年相关研究,本文从碳水化合物对肠道微生物组成的影响、肠道微生物对碳水化合物的代谢机制以及碳水化合物发酵产物短链脂肪酸对宿主的影响3个方面进行了综述。研究表明,肠道微生物可用于发酵的碳水化合物类型主要是抗性淀粉和非淀粉多糖;不同类型的碳水化合物会导致肠道菌群发生适应性变化;复杂多糖发酵产生的短链脂肪酸在调节宿主能量平衡和免疫应答方面发挥了重要作用。总结近年来相关研究,可加深对肠道菌群对宿主碳水化合物代谢贡献的理解,为哺乳动物机体健康状况的营养调控策略提供参考。     

肠道微生物基因组学与代谢组学分析联合应用的研究进展

随着肠道微生物对人类健康与疾病的作用日渐受到关注,肠道微生物的代谢作用已成为近年研究的热门领域之一。已有研究表明,将肠道微生物组学与代谢组学应用于宿主生理、疾病病理、药物药理等方面的研究具有重要价值。本文就肠道微生物基因组学和代谢组学分析联合应用的研究进展进行综述。     

单胃动物肠道微生物菌群与肠道免疫功能的相互作用

动物胃肠道栖息着大量的微生物,这些微生物及其代谢产物在营养、免疫等方面对宿主的健康有重要的意义。近年来研究发现肠道微生物与免疫系统间存在密切的交流和互作机制,尽管肠道共生菌具有定植抑制效应,但肠道微生物也可通过其特定组分刺激免疫细胞如Tregs细胞、Th17细胞的分化,肠道菌群的紊乱可能导致细菌移位、肠道屏障功能损伤,影响机体健康。宿主免疫系统可通过分泌多种免疫效应因子如MUC、sIgA、ITF、RegIIIγ、α-防御素等调节肠道微生物的分布和组成,调节肠道菌群的稳态。本文综述了单胃动物肠道微生物菌群的组成,深入探讨了肠道微生物菌群与动物肠道免疫功能之间的相互作用。     

重组微生物生理学

重组微生物生理学主要研究外源基因与宿主的相互作用以及细胞生理状态对这种相互作用的影响。宿主与外源基因的相互作用可发生在复制、分配、表达、代谢等各种水平,主要的分子机制为核酸-核酸、核酸-蛋白质的相互作用,一些小分子化合物可作为信号或效应子参与大分子的相互作用。重组微生物生理学研究主要包括下列三方面工作:1.噬菌体、质粒与宿主的相互作用以及基因工程菌中目的基因的复制、分配和表达规律。2.微生物响答系统的响答及适应的分子机制及其对外源基因调控的影响。3.细胞生长速率对宿主基因和外源基因调控的影响。这些工作融合了分子水平和细胞水平的研究,模糊了分子生物学和生理学的界限,成为基因工程的理论基础之一。美国微生物学会自1987年起把重组微生物生理学列为年会的一个独立专题。 外源基因与宿主的相互作用 噬菌体和质粒等染色体外基因与宿主基因处于一种依赖、互补和竞争的复杂关系。     

The interplay between host cellular and gut microbial metabolism in NAFLD development and prevention

Metabolism regulation centred on insulin resistance is increasingly important in nonalcoholic fatty liver disease (NAFLD). This review focuses on the interactions between the host cellular and gut microbial metabolism during the development of NAFLD. The cellular metabolism of essential nutrients, such as glucose, lipids and amino acids, is reconstructed with inflammation, immune mechanisms and oxidative stress, and these alterations modify the intestinal, hepatic and systemic environments, and regulate the composition and activity of gut microbes. Microbial metabolites, such as short-chain fatty acids, secondary bile acids, protein fermentation products, choline and ethanol and bacterial toxicants, such as lipopolysaccharides, peptidoglycans and bacterial DNA, play vital roles in NAFLD. The microbe–metabolite relationship is crucial for the modulation of intestinal microbial composition and metabolic activity. The intestinal microbiota and their metabolites participate in epithelial cell metabolism via a series of cell receptors and signalling pathways and remodel the metabolism of various cells in the liver via the gut–liver axis. Microbial metabolic manipulation is a promising strategy for NAFLD prevention, but larger-sampled clinical trials are required for future application.     

Merging chemical ecology with bacterial genome mining for secondary metabolite discovery

The integration of chemical ecology and bacterial genome mining can enhance the discovery of structurally diverse natural products in functional contexts. By examining bacterial secondary metabolism in the framework of its ecological niche, insights into the upregulation of orphan biosynthetic pathways and the enhancement of the enzyme substrate supply can be obtained, leading to the discovery of new secondary metabolic pathways that would otherwise be silent or undetected under typical laboratory cultivation conditions. Access to these new natural products (i.e., the chemotypes) facilitates experimental genotype-to-phenotype linkages. Here, we describe certain functional natural products produced by Xenorhabdus and Photorhabdus bacteria with experimentally linked biosynthetic gene clusters as illustrative examples of the synergy between chemical ecology and bacterial genome mining in connecting genotypes to phenotypes through chemotype characterization. These Gammaproteobacteria share a mutualistic relationship with nematodes and a pathogenic relationship with insects and, in select cases, humans. The natural products encoded by these bacteria distinguish their interactions with their animal hosts and other microorganisms in their multipartite symbiotic lifestyles. Though both genera have similar lifestyles, their genetic, chemical, and physiological attributes are distinct. Both undergo phenotypic variation and produce a profuse number of bioactive secondary metabolites. We provide further detail in the context of regulation, production, processing, and function for these genetically encoded small molecules with respect to their roles in mutualism and pathogenicity. These collective insights more widely promote the discovery of atypical orphan biosynthetic pathways encoding novel small molecules in symbiotic systems, which could open up new avenues for investigating and exploiting microbial chemical signaling in host–bacteria interactions.     

肠道微生物与大肠癌相关性的研究进展

越来越多的研究表明,肠道微生物可以影响大肠癌的发生发展。例如,产肠毒素脆弱拟杆菌、具核梭杆菌等已被证实与晚期的大肠癌和患者生存率降低相关。肠道微生物变化可以导致肠道稳态破坏,菌群数量以及类别的变化会导致宿主产生复杂的病理生理反应过程,促进大肠癌的发生发展。因此需要研究肠道微生物如何破坏肠道屏障、介导物质代谢、产生炎症因子及激活信号转导通路以及如何造成肠道微生物生态失调从而加速疾病进程。通过研究肠道微生物与大肠癌之间的相互作用,可以对大肠癌的早期诊断、治疗和预后有所帮助。本文就目前肠道微生物与大肠癌相关机制和前沿治疗的研究现状作一综述。     

短链脂肪酸对肠黏膜屏障的影响

肠黏膜屏障具有将致病性抗原等肠内物质与内环境隔离的功能,以维持内环境的相对稳定和机体的正常生命活动。其功能的维持依赖于人肠黏膜上皮细胞、肠道内正常菌群、肠道内分泌物和肠相关免疫细胞之间的功能协调,而其功能的发挥又受体内许多信号分子的影响。短链脂肪酸（short-chain fatty acids,SCFAs）就是其中一种重要的信号分子。SCFAs是肠道菌群的主要代谢产物之一,是肠道菌群与宿主代谢相互作用的媒介。宿主体内的SCFAs主要来自肠道菌群对膳食纤维的酵解,越来越多的研究证实,SCFAs不仅可以被肠道菌群利用,还可调节肠黏膜屏障及多种组织器官的代谢。本文主要就SCFAs对肠黏膜屏障的影响进行综述。

     

Overproduction of microbial products--facts and ideas

Overproduction of microbial metabolites is related to developmental phases of microorganisms. Inducers, effectors, inhibitors and various signal molecules play a role in different types of overproduction. Primary and secondary metabolism are interconnected. Biosynthesis of enzymes catalyzing metabolic reactions in microbial cells is controlled by well-known positive and negative mechanisms, e.g. induction, repression, catabolite repression, mechanisms controlling enzyme activity include isosteric and allosteric interactions, e.g. competitive and non-competitive inhibition, allosteric effects, molecular conversion etc. Biosynthesis of secondary metabolites is catalyzed by unaltered enzymes of primary metabolism, by altered enzymes of primary metabolism and by specific enzymes of secondary metabolism. In addition to classical mutagenesis and selection of suitable microbial cells, methods of molecular genetics are used in the overproduction of microbial products.     

微生物硫代谢及其驱动下建立的生物生态关系

硫在环境中广泛存在,是生物细胞的主要构成元素,微生物、动物和植物的硫基础代谢途径之间存在着广泛联系.本文以微生物硫代谢为主线,全面总结了硫在3类生物中的4条主要代谢途径,并重点阐明了其共性、区别及联系.微生物参与了所有硫的主要代谢,是驱动硫生物循环的主要动力.微生物异化硫还原降低了环境中甲烷的挥发,微生物、植物实施的同...     

Effects of long-term antibiotic treatment on mice urinary aromatic amino acid profiles

The gut microbiota–host co-metabolites are good indicators for representing the cross-talk between host and gut microbiota in a bi-direct manner. There is increasing evidence that levels of aromatic amino acids (AAAs) are associated with the alteration of intestinal microbial community though the effects of long-term microbial disturbance remain unclear. Here we monitored the gut microbiota composition and host–microbiota co-metabolites AAA profiles of mice after gentamicin and ceftriaxone treatments for nearly 4 months since their weaning to reveal the relationship between host and microbiome in long- term microbial disturbances. The study was performed employing targeted LC-MS measurement of AAA-related metabolites and 16S RNA sequence of mice cecal contents. The results showed obvious decreased gut microbial diversity and decreased Firmicutes/Bacteroidetes ratio in the cecal contents after long-term antibiotics treatment. The accumulated AAA (tyrosine, phenylalanine and tryptophan) and re-distribution of their downstreaming metabolites that produced under the existence of intestinal flora were found in mice treated with antibiotics for 4 months. Our results suggested that the long-term antibiotic treatment significantly changed the composition of the gut microbiota and destroyed the homeostasis in the intestinal metabolism. And the urinary AAA could be an indicator for exploring interactions between host and gut microbiota.